Process for preparing trimethylsilyloxy functionalized alkyllithium compounds

ABSTRACT

A process for producing compounds of the formula (CH 3 ) 3  SiORLi, wherein R is selected from alkyl groups containing 2 to 10 carbon atoms and aryl groups containing 6 to 10 carbon atoms, by reacting, optionally in the presence of a catalyst, in an inert atmosphere, a haloalcohol of the formula HORX, wherein R is selected from alkyl groups containing 2 to 10 carbon atoms and aryl groups containing 6 to 10 carbon atoms and X is selected from chlorine or bromine, is reacted with neat hexamethyldisilazane at a temperature between 20° C. and 200° C., optionally in the presence of a catalyst, after which the resulting product, a trimethylsilyloxyalkylhalide compound, is reacted at a temperature between 50° C. and 160° C., with powdered lithium metal, in an inert hydrocarbon medium, to produce the (CH 3 ) 3  SiORLi compound.

This application is a continuation of application Ser. No. 08/637,192,filed Apr. 8, 1996, now abandoned which is a continuation-in-part ofSer. No. 08/341,822 filed Nov. 21, 1994 U.S. Pat. No. 5,543,540 which isa continuation-in-part of Ser. No. 08/279,721 filed Jul. 25, 1994 U.S.Pat. No. 5,403,946.

The present invention concerns an improved process for preparingfunctionalized alkyllithium compounds of the formula (CH₃)₃ SiORLi,novel trimethylsilyloxy alkyllithium compounds and novel intermediatesused in the process.

Functionalized organolithium compounds have been used in organicsynthesis reactions for some time and more recently have been used asinitiators in the anionic polymerization of olefinic monomers. UnitedKingdom published patent application 2,241,239 discloses a process forproducing initiators of the formula R¹ R² R³ SiOALi wherein R¹, R² andR³ are aliphatic and aromatic radicals and A is a hydrocarbon bridginggroup. This patent recommended using a 1.5 to 6 stoichiometric excess oflithium, an excess of 6 was used in the examples, to get high yields.Reaction temperatures below 50° C. were employed because above 40° C.undesired by-products were observed.

U.S. Pat. No. 5,321,148, issued Jun. 14, 1994 discloses a process forpreparing functionalized alkyllithium compounds by reacting a fineparticle size lithium metal of not more than 300 microns averageparticle size with an organosiloxyalkyl halide of the formula R¹ R² R³SiORX wherein R¹, R² and R³ are independently selected from alkyl groupscontaining 1 to 10 carbon atoms and aryl groups containing 6 to 10carbon atoms, R is selected from alkyl groups containing 1 to 8 carbonatoms either straight chain or substituted by alkyl or aryl groups, X isselected from chlorine or bromine, the reaction temperature is above 50°C, the reaction medium is a hydrocarbon solvent and the reaction isconducted in an inert atmosphere. The precursor, R¹ R² R³ SiORX, isprepared by reaction of an omega-halo alcohol HORX with R¹ R² R³ SiCland an acid acceptor, in a hydrocarbon solvent. Compounds of the formulaR¹ R² R³ SiORX, when R¹, R² and R³ are methyl, prepared according to thedisclosed process, have been found to not uniformly lithiate, thusrequiring more halide feed and resulting in slow filtration rates andlower than expected yields.

The present invention provides a process for producing compounds of theformula (CH₃)₃ SiORLi wherein R is selected from alkyl groups containing2 to 10 carbon atoms and aryl groups containing 6 to 10 carbon atoms, byfirst reacting a haloalcohol of the formula HORX, wherein R has themeaning ascribed above and X is chlorine or bromine withhexamethyldisilazane, without solvent (neat). The resulting product, atrimethylsilyloxy-alkylhalide compound, is then reacted, in a secondprocess step, with powdered lithium metal suspended in an inert liquidhydrocarbon solvent to produce the desired trimethylsilyloxyalkyllithiumcompound. The first step of the reaction can be done at temperaturesfrom about 20° C. to 200° C.; the second step of the reaction is done ata temperature that is between 50° and 160° C. Both the first and secondstep of the process are conducted in an inert atmosphere. The firstreaction can be catalyzed by a number of catalysts, for example hydrogenchloride, trimethylsilyl chloride, succinimide, saccharin, andbarbituric acid.

Advantages of conducting the first step with no solvent include:

No solvent expense.

Faster reaction kinetics.

No need to strip solvent.

No waste solvent stream generated.

Product can be used directly in the subsequent reaction.

Extensive purification of the precursor eliminated.

Greater throughput per batch.

The haloalcohol is of the formula HORX, wherein R is selected from alkylgroups of 2 to 10 carbon atoms, straight chain or substituted by alkylor aryl groups and aryl groups containing 6 to 10 carbon atoms and X ischloro or bromo. The trimethylsilyloxyalkylhalide compounds are producedby reaction of the haloalcohol with hexamethyldisilazane, with nosolvent.

Trimethylsiloxyalkylhalides useful in the practice of this inventioninclude but are not limited to 2-(trimethylsilyloxy)-1-ethyl halide,3-(trimethylsilyloxy)-1-propyl halide,3-(trimethylsilyloxy)-2-methyl-1-propyl halide,3-(trimethylsilyloxy)-2,2-dimethyl-1-propyl halide,4-(trimethylsilyloxy)-1-butyl halide, 5-(trimethylsilyloxy)-1- pentylhalide, 6-(trimethylsilyloxy)-1-hexyl halide, (4-(trimethylsilyloxymethyl)-cyclohexyl)-1-methyl halide,8-(trimethylsilyloxy)-1-octyl halide, and the like.

The lithium metal is used in particulate or powder form of not greaterthan 300 micron average particle size and preferably 10 to 300 microns.The lithium typically contains 0.4 to 0.76 weight percent sodium and isused in at least stoichiometric amounts, preferably in excess ofstoichiometric of 1 to 100% and preferably 20 to 40% excess. The lithiumdispersion is prepared for use by washing several times with pentane orsome other hydrocarbon solvent of choice, to remove the dispersingfluid, and preferably subjected to high speed agitation at elevatedtemperatures to condition the lithium for the reaction.

The second process step, the lithiation reaction, utilizes a temperaturethat is from at least 50° C. up to just below the decompositiontemperature of the product, and preferably from 50° C. up to the boilingpoint of the solvent with reflux temperatures being most preferred. Theoptimal temperature for running the reaction can be exceeded by usingonly a high boiling solvent such as decane (BP-174° C.). The usefultemperature range for operating the process is between about 50° C. andabout 160° C. Reduced or elevated temperature can be employed if desiredbut are not required. The reactants and the products are not highlycorrosive so many materials of construction can be used for the reactorand related process equipment.

The reaction solvent is an inert, liquid, non-polar hydrocarbon solventselected from aliphatic, cycloaliphatic and aromatic hydrocarbons ormixtures thereof. Preferred solvents are aliphatic, cycloaliphatic andaromatic hydrocarbons, especially alkanes having 3 to 12 carbon atoms,cycloalkanes having 4 to 8 carbon atoms and aromatic hydrocarbons having6 to 10 carbon atoms and mixtures thereof. The inert hydrocarbon mediumincludes but is not limited to pentane, hexane, cyclopentane,cyclohexane, methylcyclopentane, methylcyclohexane, heptane,methylcycloheptane, octane, decane, toluene, ethylbenzene, p-xylene,m-xylene, o-xylene, n-propylbenzene, 2-propylbenzene, n-butylbenzene,and t-butylbenzene, and mixtures thereof.

According to the process of the present invention, the precursortriorganosiloxyalkyl halide was prepared neat from the correspondingomega halo-alcohol, and hexamethyldisilazane. The lithium metaldispersion, when prepared in mineral oil, is washed free of mineral oilwith a liquid hydrocarbon solvent, dried in a stream of argon andtransferred to the reaction vessel with the hydrocarbon solvent. Themixture of clean metal and liquid hydrocarbon solvent was heated to thereaction temperature and the functionalized triorganosiloxyalkyl halidewas added slowly to the heated lithium metal-hydrocarbon solventmixture. An exotherm developed after 5-30% of the halide was added. Thereaction temperature was controlled by external cooling of the reactionmixture. At the end of the halide feed, the reaction temperature rapidlydeclined to room temperature. The reaction mixture was stirred severalhours at room temperature. At the end of the lithiation reaction, thereaction mixture was transferred to a sintered glass filter throughwhich the solution was filtered rapidly with 3 psi (20.68×10³ Pa) argonpressure. After the insolubles were removed by filtration, the filtratewas an essentially pure solution of the trimethylsiloxyalkyllithiumcompound. The resultant non-turbid solution was analyzed for total base,active carbon-lithium (modified Watson-Estham titration) and inorganichalide.

Trimethylsilyloxyalkyl lithium compounds which can be prepared by theprocess of this invention include but are not limited to3-(trimethylsilyloxy)-1-propyl lithium,3-(trimethylsilyloxy)-2-methyl-1-propyl lithium,4-(trimethylsilyloxy)-1-butyl lithium, 5-(trimethylsilyloxy)-1-pentyllithium, 6-(trimethylsilyloxy)-1-hexyl lithium,(4-(trimethylsilyloxymethyl)-cyclohexyl)-1-methyl lithium, 8-(trimethylsilyloxy)-1-octyl lithium and the like.

The following examples further illustrate the invention.

PREPARATION OF HALOORGANOSILYLOXYALKANE MATERIALS 1. Preparation of3-Chloro-2,2-dimethyl-1-trimethylsilyloxy-propane at 150° C., Lot 9277

A 500 milliliter, three-necked flask was fitted with a large magneticstir bar, a reflux condenser, a thermocouple attached to aTHERM-O-WATCH®, a 125 ml. pressure-equalizing addition funnel, and anargon inlet. This apparatus was dried in an oven overnight at 125° C.,assembled hot, and allowed to cool to room temperature in a stream ofargon. The flask was charged with 122.58 grams (1.00 mole, 1.00equivalent) of 3-chloro-2,2-dimethyl-1-propanol. Hexamethyldisilazane,83.24 grams (0.516 mole, 0.516 equivalent), was then added rapidlydropwise via the addition funnel. Trimethylsilylchloride catalyst, oneml., was added via a syringe. An immediate exotherm of 21.7° C. wasobserved. A white precipitate also formed when the catalyst was added.The reaction mixture was heated to 150° C. with a heating mantle,controlled by the THERM-O-WATCH®. After ninety minutes at thistemperature, all the solids had dissolved. The heat source was removed.The reaction mixture was analyzed by Gas Chromatography (GC), thirtymeter X 0.53 mm AT-1 column. All the starting3-chloro-2,2-dimethyl-1-propanol had been consumed, with the formationof a single, higher-boiling component. After the reaction mixture hadcooled to room temperature, it was transferred to a medium porositysintered glass filter. The filtrate was collected in a dry 250 ml.bottle. This afforded a clear, very pale yellow solution, yield=188.84grams (97.0% yield). GC assay=97.5% desired product, and 2.5% unknowns.

2. Preparation of 3-Chloro-2,2-dimethyl-1-trimethylsilyloxy-propane at100° C, Lot 9279

A 500 milliliter, three-necked flask was fitted with a large magneticstir bar, a reflux condenser, a thermocouple attached to aTHERM-O-WATCH®, a 125 ml. pressure-equalizing addition funnel, and anargon inlet. This apparatus was dried in an oven overnight at 125° C.,assembled hot, and allowed to cool to room temperature in a stream ofargon. The flask was charged with 122.68 grams (1.00 mole, 1.00equivalent) of 3-chloro-2,2-dimethyl-1-propanol. Hexamethyldisilazane,83.35 grams (0.516 mole, 0.516 equivalent), was then added dropwise viathe addition funnel. Trimethylsilylchloride catalyst, one ml., was addedvia a syringe. An immediate exotherm of 23.4° C. was observed. A whiteprecipitate also formed when the catalyst was added. The reactionmixture was heated to 100° C with a heating mantle, controlled by theTHERM-O-WATCH®. Periodically, an aliquot was removed, filtered through a0.45 micron syringe filter, and analyzed by Gas Chromatography (GC),thirty meter X 0.53 mm AT-1 column. After twenty-four hours at 100° C.,both of the starting materials were still present. Therefore, anadditional 0.5 ml. of trimethylsilylchloride was added. Afterforty-eight hours at 100° C, both of the starting materials were stillpresent. Therefore, an additional 0.5 ml. of trimethylsilylchloride wasadded. After a total of seventy-two hours at 100° C, all the starting3-chloro-2,2-dimethyl-1-propanol had been consumed, with the formationof a single, higher-boiling component. The heat source was removed.After the reaction mixture had cooled to room temperature, it wastransferred to a medium porosity sintered glass filter. The filtrate wascollected in a dry 250 ml. bottle. This afforded a clear, very paleyellow solution, yield=178.37 grams (91.65% yield). GC assay=96.8%desired product, 0.1% hexamethyldisilazane, and 3.1% unknowns.

B. PREPARATION OF TRIMETHYLSILYLOXYALKYLLITHIUM COMPOUNDS 1. Preparationof 2,2-Dimethyl-3-trimethylsilyloxy-1-propyllithium Lot 9291

A 500 ml., three-necked flask was equipped with a mechanical stirrer, a125 ml. pressure-equalizing addition funnel, and a Claisen adapterfitted with a dry ice condenser, a thermocouple, and an argon inlet.This apparatus was dried in an oven overnight at 125° C., assembled hot,and allowed to cool to room temperature in a stream of argon. Lithiumdispersion was washed free of mineral oil with hexane (2×70 ml.), andpentane (1×70 ml.), then dried in a stream of argon. The dry lithiumpowder, 6.80 grams (0.980 mole, 2.80 equivalents) was transferred to thereaction flask with 280 ml. cyclohexane. This slurry was stirred at 450RPMs, and heated to 64.7° C. with a heating mantle. The heat source wasremoved. 3-Chloro-2,2-dimethyl-1 -trimethylsilyloxy-propane, 68.10 grams(Lot 9277, 0.350 mole, 1.00 equivalent) was then added dropwise to thereaction mixture. An exotherm was noted after 12.3% of the feed had beenadded. A dry ice/hexane cooling bath was employed to maintain thereaction temperature at 60-65° C. The total halide feed time waseighty-five minutes. The reaction temperature rapidly fell off at theend of the halide feed. The reaction mixture was stirred at roomtemperature for seventy minutes, then transferred to a small, sinteredglass filter. The product filtered rapidly with 2 psi argon. The mudswere reslurried with cyclohexane (2×60 ml.). This afforded a pale yellowsolution, yield=450 ml., 352.05 grams.

Total base=15.6 wt. %.

Active C-Li=15.3 wt. %.

Soluble chloride=182 ppm.

Yield based on active C-Li=92.6%.

2. Preparation of 2,2-Dimethyl-3-trimethylsilyloxy-1-propyllithium Lot9295

A 500 ml., three-necked flask was equipped with a mechanical stirrer, a125 ml. pressure-equalizing addition funnel, and a Claisen adapterfitted with a dry ice condenser, a thermocouple, and an argon inlet.This apparatus was dried in an oven overnight at 125° C., assembled hot,and allowed to cool to room temperature in a stream of argon. Lithiumdispersion was washed free of mineral oil with hexane (2×70 ml.), andpentane (1×70 ml.), then dried in a stream of argon. The dry lithiumpowder, 6.50 grams (0.936 mole, 2.80 equivalents) was transferred to thereaction flask with 280 ml. cyclohexane. This slurry was stirred at 450RPMs, and heated to 64.7° C. with a heating mantle. The heat source wasremoved. 3-Chloro-2,2-dimethyl-1-trimethylsilyloxy-propane, 65.09 grams(Lot 9277, 0.334 mole, 1.00 equivalent) was then added dropwise to thereaction mixture. An exotherm was noted after 9.6% of the feed had beenadded. A dry ice/hexane cooling bath was employed to maintain thereaction temperature at 60-65° C. The total halide feed time wasninety-one minutes. The reaction temperature rapidly fell off at the endof the halide feed. The reaction mixture was stirred at room temperaturefor ninety minutes, then transferred to a small, sintered glass filter.The product filtered rapidly with 2 psi argon. The muds were reslurriedwith cyclohexane (2×50 ml.). This afforded a pale yellow solution,yield=430 ml., 335.10 grams.

Total base=15.5 wt. %.

Active C-Li=15.3 wt. %.

Yield based on active C-Li=92.4%.

C. COMPARATIVE EXAMPLE 1. Preparation of3-Chloro-2,2-dimethyl-1-trimethylsilyloxy-propane in CyclohexaneSolution, Lot 9103

A one liter, three-necked flask was fitted with a large magnetic stirbar, a reflux condenser, a teflon clad thermocouple, a 125 ml.pressure-equalizing addition funnel, and an argon inlet. This apparatuswas dried in an oven overnight at 125° C., assembled hot, and allowed tocool to room temperature in a stream of argon. The flask was chargedwith 122.60 grams (1.00 mole, 1.00 equivalent) of3-chloro-2,2-dimethyl-1-propanol, and 250 ml. of cyclohexane. Thisafforded a homogenous solution. Hexamethyldisilazane, 85.54 grams (0.53mole, 0.53 equivalent) was then added dropwise. There was an initialendotherm, then the temperature slowly elevated. Total feed time wasseventy minutes. The catalyst, trimethylsilylchloride (0.5 ml.) was thenadded with a pipette. A white precipitate formed immediately. Thereaction flask was swept with a slight positive flow of argon, above thelevel of the liquid. The reaction mixture was heated to reflux with aheating mantle. Ammonia fumes were detected exiting from the apparatuswith pH paper before reflux was achieved. After three hours at reflux,the reaction mixture was clear and homogenous. After five and a halfhours heating, the heat source was removed. After six hours, an aliquotwas removed, and analyzed by Gas Chromatography (GC), thirty meter X0.53 mm AT-1 column. The conversion to the desired product was 64.2%.The reaction mixture was again heated to reflux, and held at refluxovernight. In the morning, the heat source was again removed, and thereaction was reanalyzed by GC. Very little change in composition wasdetected by GC. 3-Chloro-2,2-dimethyl-1-propanol andhexamethyldisilazane were both still present in the reaction mixture.Therefore, an additional 0.5 ml. of trimethylsilylchloride was added tothe reaction flask. A white precipitate was again observed. The reactionmixture was heated to reflux for an additional six hours, then allowedto cool to room temperature. All the starting material had beenconsumed. The reaction mixture was transferred to a dry, 500 ml.single-necked flask. The product was purified by distillation through asix inch Vigreux column.

The desired product had a boiling point of 169.8-175.0° C.

This afforded a clear, colorless oil, yield=183.07 grams, 94.1%.

GC analysis of this material indicated it was 98.9% desired product,0.6% hexamethyldisilazane, and 0.5% unknowns.

The comparison example shows the superiority of performing thetrimethylsilation reaction without solvent. The neat reaction featuredfaster reaction rates, easier work-up, and no need for extensive productpurification by distillation.

I claim:
 1. A trimethylsilyloxyalkyl halide of the formula (CH₃)₃ SiORXwherein R is selected from branched or cyclic alkyl groups containing 3to 10 carbon atoms and aryl groups containing 6 to 10 carbon atoms and Xis selected from bromide and chloride, wherein said branched or cyclicalkyl groups further comprise at least 3 carbon atoms bridging O and X.2. A trimethylsiloxyalkyl halide of claim 1 wherein thetrimethylsiloxyalkyl halide is selected from the group consisting of3-(trimethylsiloxy)-2-methyl-1-propyl halide,(4-(trimethylsiloxy)-cyclohexyl)-1-methyl halide, and3-(trimethylsiloxy)-2,2-dimethyl-1-propyl halide.
 3. Atrimethylsilyloxyalkyl halide of claim 2 wherein the halide is selectedfrom the group consisting of chloride and bromide.
 4. Atrimethylsilyloxyalkyl lithium compound of the formula (CH₃)₃ SiORLiwherein R is selected from alkyl groups containing 3 to 10 carbon atomsand aryl groups containing 6 to 10 carbon atoms.
 5. Atrimethylsilyloxyalkyl lithium compound of claim 4 wherein thetrimethylsilyloxyalkyl lithium compound is selected from the groupconsisting of 3-(trimethylsilyloxy)-1-propyl lithium,3-(trimethylsilyloxy)-2-methyl- 1-propyl lithium,4-(trimethylsilyloxy)-1-butyl lithium, 5-(trimethylsilyloxy)-1-pentyllithium, 6-(trimethylsilyloxy)-1-hexyl lithium,(4-(trimethylsilyloxymethyl)-cyclohexyl)-1-methyl lithium and8-(trimethylsilyloxy)-1-octyl lithium.
 6. A trimethylsilyloxyalkylhalide product of the formula (CH₃)₃ SiORX, wherein R is selected fromthe group consisting of branched or cyclic alkyl groups containing 3 to10 carbon atoms and aryl groups containing 6 to 10 carbon atoms, and Xis selected from bromide and chloride, wherein said branched or cyclicalkyl groups contain at least 3 carbon atoms bridging O and X, producedby a process comprising reacting, in an inert atmosphere, a haloalcoholof the formula HORX, wherein R and X are as defined above with neathexamethyldisilazane at a temperature between 20° C. and 200° C.,optionally in the presence of a catalyst.
 7. The product of the processof claim 6 further comprising employing an effective amount of acatalyst in the reaction.
 8. The product of the process of claim 7wherein the catalyst is selected from the group consisting of hydrogenchloride, trimethylsilyl chloride, succinimide, saccharin, andbarbituric acid.
 9. The product of the process of claim 6 wherein theomega- halo alcohol is reacted neat with hexamethyldisilazane at atemperature between 100° C and 180° C.